"Stair Step Study"

NCT03309176 | Completed Phase 4

• 1 other identifier: NL56254.091.15
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

Rationale: There is some information suggesting that a progesterone-induced withdrawal bleeding before the start of ovulation induction in women suffering from oligo- or amenorrhea reduces pregnancy and live birth rate. Objective: To evaluate the effects of withholding progesterone-induced endometrial withdrawal bleeding before ovulation induction on the time to pregnancy and the ongoing pregnancy rate. Study design: Prospective multicenter randomized controlled feasibility study Study population: Women with oligomenorrhea or amenorrhea according to WHO classification category 2 Intervention: Patients will be randomized to receive one of the following two treatments: Stair step group: blind start ovulation induction (no progesterone induced withdrawal bleeding and stair step protocol in case of treatment failure. Control: standard care; a progesterone induced withdrawal bleeding in case of no spontaneous menses before starting an ovulation induction cycle and in between anovulatory cycles. Main study parameters/endpoints: The primary endpoints are the time to pregnancy and ongoing pregnancy rate within a treatment horizon of 3 cycles. Secondary endpoints include time to ovulation, endometrial thickness, multiple pregnancy and the incidence of treatment failure. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The number of site visits or physical examinations will not differ from accepted clinical practice.

Conditions

Ovulation Disorder

Outcome Measures

Primary Outcomes (2)

• Ongoing pregnancy rate per cycle

  Ongoing pregnancy is defined as the presence of at least one intra uterine fetus with heartbeat at 8 weeks of gestation

  in case of pregnancy: 8 weeks after the start of each cycle, (maximum of 3 cycles, duration of 1 cycle: 28-35 days)

• Time to pregnancy

  the time between obtaining informed consent and the presence of a positive pregnancy test after treatment

  duration of 1 cycle: 28-35 days, a maximum of 3 cycles will be performed (pregnancy test will be performed at the end of the cycle if there is no menstruation)

Secondary Outcomes (7)

• Time to ovulation

  3 cycles of 28-35 days, calculated as 14 days before the start of menstruation or 14 days before a positive pregnancy test

• Endometrial thickness on the last day of ultrasonography

  maximum of 3 cycles (each 28-35 days)

• The incidence of multiple follicle growth on the last day of ultrasonography

  maximum of 3 cycles (each 28-35 days)

• The incidence of multiple pregnancy

  in case of pregnancy: 8 weeks after the start of a treatment cycle (maximum of 3 cycles; each 28-35 days)

• The incidence of treatment failure

  maximum of 3 cycles (each 28-35 days)

Study Arms (2)

Standard group

ACTIVE COMPARATOR

Intervention:Medroxyprogesterone acetate (Provera) 10 mg daily for 10 days will be used prior to starting ovulation induction with clomiphene citrate (CC) and between anovulatory cycles. On cycle day (CD) 3 CC 50 mg is administered daily for 5 days. Follicle growth will be monitored by ultrasound, starting from CD11. Anovulatory patients (defined as no follicle ≥ 14 mm) on CD20, will receive Provera 10mg daily for 10 days. The CC dosage will be increased in the next cycle. On CD3 patients will receive CC 100 mg daily for 5 days with ultrasounds performed from CD11 onwards. Anovulatory patients will receive Provera 10mg daily for 10 days. In the next cycle the CC dose will be increased to 150 mg, starting from CD3, daily for 5 days with ultrasounds starting from CD11-20.

Drug: Medroxyprogesterone Acetate 10 MG

Stair Step group

EXPERIMENTAL

Intervention: Stair step protocol without medroxyprogesterone acetate 10 mg prior to ovulation induction with clomiphene citrate (CC), nor in between anovulatory cycles. After performing an ultrasound to check for the presence of cysts or any other abnormalities and a negative pregnancy test, patients will receive CC 50 mg daily for 5 days. Ultrasounds will be performed on CD11-14. If there is no response on CD14 (no follicle ≥ 14 mm), the dose of CC is immediately increased to 100 mg CC daily for 5 days and an ultrasound is performed 1 week following the last ultrasound. If there is no response, 150 mg CC daily is initiated immediately for 5 days and the ultrasound is repeated 1 week after the previous ultrasound.

Other: Stair step protocol without Medroxyprogesterone Acetate

Interventions

Medroxyprogesterone Acetate 10 MG DRUG

Patients in the standard arm will receive Medroxyprogesterone Acetate 10mg daily for 10 days prior to the first ovulation induction cycle and in between anovulatory cycles.

Also known as: Provera

Standard group

Stair step protocol without Medroxyprogesterone Acetate OTHER

No administration of Medroxyprogesterone Acetate prior to each cycle. Stair step method: rapidly increasing the dose of clomiphene citrate in case of no follicular response

Also known as: Stair step

Stair Step group

Eligibility Criteria

• Age: 18 Years - 41 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• WHO classification category 2 PCOS or non-PCOS
• Age between 18 - 41 years
• Patent Fallopian tubes, proven by hysterosalpingography (HSG), a negative Chlamydia antibody titre (CAT) or diagnostic laparoscopy combined with tubal testing (DLS and TT), depending on the local protocol.
• BMI \< 40 kg/m2

You may not qualify if:

• BMI \> 40 kg/m2
• Previous unsuccessful ovulation induction cycles with CC
• Double-sided tubal pathology
• Presence of ovarian cysts on ultrasound
• Moderate - severe male infertility (TMSC \< 3 million)
• Grade III/IV endometriosis
• Thrombosis
• Severe liver disease

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (3)

Gelderse Vallei Hospital

Ede, Gelderland, Netherlands

Location

Canisius-Wilhelmina Hospital

Nijmegen, Gelderland, Netherlands

Location

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Location

MeSH Terms

Interventions

Medroxyprogesterone Acetate

Intervention Hierarchy (Ancestors)

Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Stair step group: blind start ovulation induction (no progesterone induced withdrawal bleeding and stair step protocol in case of treatment failure. Control: standard care; a progesterone induced withdrawal bleeding in case of no spontaneous menses before starting an ovulation induction cycle and in between anovulatory cycles.

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: October 13, 2017
• Study Start: June 21, 2016
• Primary Completion: November 30, 2017
• Study Completion: May 31, 2018
• Last Updated: June 6, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)